Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki-67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus.

Abstract

Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki-67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region-difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki-67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression.

• Authors: Jianlong He, Xiaoying Ji, Yongfei Li, Xiaochang Xue, Guodong Feng, Huqin Zhang, Huichun Wang, Meilii Gao
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) 2016 Feb-Mar Vol. 68 Issue 2-3 Pg. 149-56 ISSN: 1618-1433 [Electronic] Germany
• PMID: 26679980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Ki-67 Antigen
• Mki67 protein, mouse
• Nuclear Proteins
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Benzo(a)pyrene
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apoptosis Regulatory Proteins (genetics)
• Benzo(a)pyrene (toxicity)
• Caspase 3 (genetics)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Dose-Response Relationship, Drug
• Gene Expression (drug effects)
• Hippocampus (drug effects, metabolism, pathology)
• Immunohistochemistry
• Ki-67 Antigen (genetics)
• Mice, Inbred ICR
• Nuclear Proteins (genetics)
• Organ Size (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Proto-Oncogene Proteins c-myc (genetics)
• Tumor Suppressor Protein p53 (genetics)
• bcl-2-Associated X Protein (genetics)